The rat gastric fistula preparation has been developed and validated for studying the effects of acute and chronic administration of sedative hypnotics. Using a Behavioral Rating Scale and Respiratory Depression, it was found that secobarbital was somewhat more potent and methaqualone about 1/5 as potent as pentobarbital as a depressant. In this determination valid bioassays were obtained as indicated by the fact that the slopes of the dose response curves for these three drugs were not different. These drugs were also compared to diazepam which had a gentler slope and exhibited a ceiling effect. They were also compared to chloral hydrate, whose dose response curve had a slope significantly steeper than pentobarbital's. Chloral hydrate did not, however, produce any respiratory depression nor did diazepam whereas pentobarbital, secobarbital and methaqualone produced a dose-related depression of respiratory rate. Interaction studies between alcohol, pentobarbital and diazepam have been conducted. These data indicate that the interaction between alcohol and diazepam and alcohol and pentobarbital are less then additive, and that the degree of interaction was a function of the doses of alcohol, pentobarbital and diazepam.